Beta-phenyl, beta-alkyl isopropyl amines



Patented eb. 5, 1946 UNITED STATES PATENT OFFICE 2,394,092 p-PHENYL, fl-ALKYL rsoraorvr. AMINES Fred P. Nabenhauer, Somerton, Pa., assignor to Smith, Kline &- French Laboratories, Philadelphia. Pa., a corporation of Pennsylvania No Drawing. Application June 7, 193a, Seriai No. 212.391

6 Claims. (CI. 260-5703) be useful, for example, as an intermediate for the preparation of various chemical compounds such, for example, as isoquinoline compounds.

More particularly, from the therapeutic standpoint the new composition in accordance with this invention in various forms will be found to be advantageous; for producing effects simulating stimulation of the sympathetic nervous system and for effecting contraction or relaxation of smooth muscle depending upon the function of the sympathetic nervous system; for effecting vasoconstriction, and for producing general and local efiects resultant therefrom, respectively. In general, the effects produced adapt it for the treatment of any condition where general or local effects resultant from affecting the sympathetic nervous system, are therapeutically effective and desirable.

From the broad standpoint the composition contemplated by this invention will comprise cerwhere R." and R, respectively are either a methyl,

ethyl, propyl or isopropyl group, and R is hydrogap or a methyl group; and organic and inorganic salts of said compounds.

From the therapeutic standpoint the bases comprising the primary and secondary amines disclosed above will have advantages as indicated, as

will also the non-toxic organic and inorganic salts thereof, produced with organic and inorganic acids yielding non-toxic ionaas for ex,-

ample, the hydrochlorides, sulphates, oleates,

tartrates, etc.

From the more specific standpoint generally an from the therapeutic standpoint broadly,"th'is invention will be made apparent by the following structural formula:

' on-cm-cm H: NH 1 solution in a light mineral oil to a concentration of, for example, 0.25-5.0%. The non-toxic salts will lend themselves to extension in water, as in aqueous solution. The bases may be locally applied, for example, to the mucosa, in vapor form by inhalation extended with air.

will be made obviousby the following illustration for the preparation of specific primary and secondary amines and salts thereof.

By way of general illustration, the composition in accordance with this invention from the broad and specific standpoints may be effectively prepared by treating a ketone of the following structure:

wherein R." is an alkyl group, as methyl (CHa). ethyl. (C2Hs) propyl (CaH-l) etc., with formamide,

.or for the production of N-methyl derivatives with N-methy'l formamide, thereby obtaining-the corresponding formyl derivative, hydrolyzing to the amine salt and liberating the salt from its solution with alkali.

- Where a salt of the base, or of the N-methyl derivative thereof is to be prepared, such may be readily accomplished by neutralizing the base' with a suitable acid, as hydrochloric, oleic, tartaric, sulphuric. etc.

By way of more specific illustration, for example, p-phenyl, p-methyl isopropyl amine may be prepared from phenyl methyl acetone by adding to 1 mole of phenyl methyl acetone moles of formamide at a temperature of about 150-l70 C. The reaction, which will result in the production of the formyl derivative, will proceed as follows:

The formyl derivative will be hydrolyzed in any well known manner, such as with constant boiling hydrochloric acid and water to produce the amine salt which will have the following formula:

CH: H I

JJ-(s-UH: H 1 :11.

The base when separated and dried boils at 216 C.

For the preparation of the N-methyl derivative of, for example, p-phenyl, p-methyl isopropyl amine, the above procedure will be followed, ex cept that N-methyl formamide will be used,in place of formamide. The N-methyl derivative so prepared boils within the range 2l4-220 C.

The salts of the base, as hydrochlorides, sulphates, etc. and of the N-methyl derivatives thereof may be readily prepared by neutralizing with a suitable acid, as hydrochloric, oleic, tartaric, sulphuric, etc. i

In using the broad and specific embodiments of this invention for therapeutic effect, generally speaking the bases will be used locally, while the salts, which may also be used locally, will be preferable for oral or parenteral administration. The compounds may be conveniently extended for use, either by admixture with an excipient, as lactose or other suitable excipient, or a solvent. as water, in the case of the salts, or an oil, as a mineral or vegetable oil in the case of the bases. Thus, for example, the p-phenyl, p-alkyl iso- 'propyl amines. and the N-methyl derivatives traction of smooth muscle. or general systemic 76 vasoconstriction. aqueous solutions of the salts of the fl-phenyl, p-alkyl isopropyl amines or of the N methyl derivatives thereof, may be parenterally administered and such may be orally administered, or if desired, the compounds may be administered in tablet form in admixture with any suitable excipient, as for example, lactose, sucrose, starch, etc., together with a binder, as for example, gelatin.

In use of the new composition in accordance with this invention for medicinal function or therapeutic effect the dosage or amount administered will depend upon a number of factors. Thus, particular dosage will depend upon the condition of the patient to be relieved, the quantitative or qualitative efiect to be produced, the specific composition selected for administration, the mode of administration and the patients individual reaction to the particular composition and mode of administration.

This application is a continuation in part of an application filed by me, Serial No. 143,939, filed May 21, 1937, and an application filed by me, Serial No. 92,847, filed July 27, 1936.

What I claimand desire to protect by letters Patent is:

1. A medicinal remedy for application to the nasal mucosa to produce shrinkage thereof without producing affect upon the central nervous system, comprising essentially a compound from the group consisting of compounds having the following formula:

- cB-orLcm HIE where R is a member of the group consisting of hydrogen and a methyl group and non-toxic salts of said compounds.

2. A medicinal remedy for application to the nasal mucosa to produce shrinkage thereof without producing affect upon the central nervous system, comprising essentially a compound from the group consisting of compounds having the following formula:

CH-(|3H.CH|

7 and non-toxic salts thereof.

4. Av compound from the group consisting of compounds having the formula:

hydrogen and a methyl group; and salts of said awww 3 where R is a. member of the group consisting of 8. The mmmzmd. mm m mrmula:

@ompounds.

5. The compound having the formula: 

